Objective of this Phase-1 SBIR (1st resubmission/amended) project is: to implement and test an imaging method incorporating an improved quantitative ultrasound backscatter (QUBS) method, which uses scatterer size imaging (SSI) and acoustic scatterer concentration (ASC) for detection of breast cancer. Past SSI and ASC images were known in many cases to separate cancerous from benign tumors even without these improvements. The Research Design to combine QUBS with inverse scattering tomography (IST) and reflection tomography (RT) into a hybrid method. IST will correct RT images for refraction and attenuation. The corrected RT data will be used to make corrected and compounded QUBS images of greater accuracy, precision, and spatial resolution than possible previously. IST and RT are the two components of the ultrasound imaging method developed by TechniScan, Inc. (TSI), which is known as UltraSound-CTTM (i.e., USCT). USCT reconstructs an image using scattered data from views spaced a full 360[unreadable]around the object under study. IST is based on modeling ultrasound propagation through tissue using an exact wave equation model (EWEM) rather than a ray-based approach, which is the basis of common ultrasound imaging. Only EWEMs can produce high resolution (to 3/4 mm), quantitative images of sound speed, absorption and density gradient and can account for the effects of multiple scattering, refraction, diffraction, attenuation and reflection losses. RT imaging uses IST to correct for refraction and absorption (but not for multiple scattering or diffraction). RT is partially quantitative and provides high spatial resolution (to 1/4 mm). The Research methods: to combine QUBS with IST and RT by the following steps: (1) produce an IST image of the breast; (2) collect data to produce a RT image of the breast; (3) then make a refraction attenuation corrected RT image; (4) use these same corrections to make a spatially compounded, refraction corrected, attenuation corrected QUBS image of the breast. The QUBS image will be derived by processing this corrected data with particular algorithms that yield the improved scatterer size image (SSI). The Specific Aims to implement the Research Design and Methods are: (Aim 1) simulate QUBS algorithm performance (SSI and ACS) performance under the Born approximation using simulated data; (Aim 2) create agar phantoms to be scanned; analyze the performance of IST/RT enhanced SSI/ACS using data from simulations and from phantoms and tissue; (Aim 3) prepare to submit a Phase-2 SBIR with improved hardware that will test the synergy of a hybrid method combining QUBS with USCT to create 5 images (3 + 2 = 5), and thereby a 5-dimensional feature space for improved tissue characterization (sensitivity and specificity). One in every 7 women will develop breast cancer in her lifetime. However, present diagnostic specificity for cancer detection (using mammography) is poor, with 3 in 4 biopsies yielding benign tissue and missing about 10% of cancers. This proposal, which combines two novel techniques for breast cancer detection-namely Quantitative Ultrasound Backscatter (QUBS) and Ultrasound Inverse Scattering Tomography (IST)-has a tremendous potential for improving breast cancer detection. [unreadable] [unreadable] [unreadable]